Overexpression of a nuclear receptor HR96 contributes to spirodiclofen susceptibility in Panonychus citri (McGregor).

The citrus red mite, Panonychus citri, is one of the most notorious and devastating citrus pests around the world that has developed resistance to multiple chemical acaricides. In previous research, we found that spirodiclofen-resistant is related to overexpression of P450, CCE, and ABC transporter genes in P. citri. However, the regulatory mechanisms of these detoxification genes are still elusive. This study identified all hormone receptor 96 genes of P. citri. 8 PcHR96 genes contained highly conserved domains. The expression profiles showed that PcHR96h was significantly upregulated in spirodiclofen resistant strain and after exposure to spirodiclofen. RNA interference of PcHR96h decreased expression of detoxification genes and increased spirodiclofen susceptibility in P. citri. Furthermore, molecular docking, heterologous expression, and drug affinity responsive target stability demonstrated that PcHR96h can interact with spirodiclofen in vitro. Our research results indicate that PcHR96h plays an important role in regulating spirodiclofen susceptibility and provides theoretical support for the resistance management of P. citri.

Loss of SUN1 function in spermatocytes disrupts the attachment of telomeres to the nuclear envelope and contributes to non-obstructive azoospermia in humans.

One of the most severe forms of infertility in humans, caused by gametogenic failure, is non-obstructive azoospermia (NOA). Approximately, 20-30% of men with NOA may have single-gene mutations or other genetic variables that cause this disease. While a range of single-gene mutations associated with infertility has been identified in prior whole-exome sequencing (WES) studies, current insight into the precise genetic etiology of impaired human gametogenesis remains limited. In this paper, we described a proband with NOA who experienced hereditary infertility. WES analyses identified a homozygous variant in the SUN1 (Sad1 and UNC84 domain containing 1) gene [c. 663C > A: p.Tyr221X] that segregated with infertility. SUN1 encodes a LINC complex component essential for telomeric attachment and chromosomal movement. Spermatocytes with the observed mutations were incapable of repairing double-strand DNA breaks or undergoing meiosis. This loss of SUN1 functionality contributes to significant reductions in KASH5 levels within impaired chromosomal telomere attachment to the inner nuclear membrane. Overall, our results identify a potential genetic driver of NOA pathogenesis and provide fresh insight into the role of the SUN1 protein as a regulator of prophase I progression in the context of human meiosis.

Iron(III)-(1,10-Phenanthroline) Complex Can Enhance Ferrate(VI) and Ferrate(V) Oxidation of Organic Contaminants via Mediating Electron Transfer.

Recent research has primarily focused on the utilization of reductants as activators for Fe(VI) to generate high-valent iron species (Fe(IV)/Fe(V)) for the degradation of emerging organic contaminants (EOCs). However, a significant drawback of this approach arises from the reaction between reductants and ferrates, leading to a decrease in oxidation capacity. This study introduces a novel discovery that highlights the potential of the iron(III)-(1,10-phenanthroline) (Fe(III)-Phen) complex as an activator, effectively enhancing the degradation of EOCs by Fe(VI) and augmenting the overall oxidation capacity of Fe(VI). The degradation of EOCs in the Fe(VI)/Fe(III)-Phen system is facilitated through two mechanisms: a direct electron transfer (DET) process and electron shuttle action. The DET process involves the formation of a Phen-Fe(III)-Fe(VI)* complex, which exhibits a stronger oxidation ability than Fe(VI) alone and can accept electrons directly from EOCs. On the other hand, the electron shuttle process utilizes Fe(III)-Phen as a redox mediator to transfer electrons from EOCs to Fe(VI) through the Fe(IV)/Fe(III) or Fe(IV)/Fe(II)/Fe(III) cycle. Moreover, the Fe(III)-Phen complex can improve the utilization efficiency of Fe(V) by preventing its self-decay. This study's findings may present a viable option for utilizing an effective catalyst to enhance the oxidation of EOCs by Fe(VI) and Fe(V).

Selective Removal of Emerging Organic Contaminants from Water Using Electrogenerated Fe(IV) and Fe(V) under Near-Neutral Conditions.

Fe(IV) and Fe(V) are promising oxidants for the selective removal of emerging organic contaminants (EOCs) from water under near-neutral conditions. The Fe(III)-assisted electrochemical oxidation system with a BDD anode (Fe(III)-EOS-BDD system) has been employed to generate Fe(VI), while the generation and contributions of Fe(IV) and Fe(V) have been largely ignored. Thus, we examined the feasibility and involved mechanisms of the selective degradation of EOCs in the Fe(III)-EOS-BDD system under near-neutral conditions. It was found that Fe(III) application selectively accelerated the electro-oxidation of phenolic and sulfonamide organics and made the oxidation system be resistant to interference from Cl-, HCO3-, and humic acid. Several lines of evidence indicated that EOCs were decomposed via direct electron-transfer process on the BDD anode and by Fe(IV) and Fe(V) but not Fe(VI), besides HO•. Fe(VI) was not generated until the exhaustion of EOCs. Furthermore, the overall contributions of Fe(IV) and Fe(V) to the oxidation of phenolic and sulfonamide organics were over 45%. Our results also revealed that Fe(III) was oxidized primarily by HO• to Fe(IV) and Fe(V) in the Fe(III)-EOS-BDD system. This study advances the understanding of the roles of Fe(IV) and Fe(V) in the Fe(III)-EOS-BDD system and provides an alternative for utilizing Fe(IV) and Fe(V) under near-neutral conditions.

Current attitudes toward carrier screening for spinal muscular atrophy among pregnant women in Eastern China.

Spinal muscular atrophy (SMA) is an autosomal recessive and often fatal neurological disease. However, very little is known about the attitudes toward SMA carrier screening among Chinese pregnant people. In this study, pregnant women in Eastern China who were undergoing routine chromosomal screening programs were invited to view an educational video about SMA and complete a 26-item survey regarding their attitudes toward SMA screening by scanning a specific quick response code. A total of 1673 questionnaires were collected, and 81.1% of respondents were willing to undergo self-funded screening. If the screening program were included in the medical insurance, 97.8% of respondents were willing to accept screening. The important reasons for supporting SMA screening were a belief that it could help them make better reproductive decisions and avoid having a child with SMA. The key reason for declining SMA screening was not having a family history of genetic diseases. A higher score for SMA genetics knowledge was associated with a greater willingness to undergo SMA screening. We concluded that pregnant women in Eastern China had positive attitudes toward SMA carrier screening. Improving genetic knowledge and including the screening program in medical insurance would support the widespread implementation of SMA carrier screening. Steps should be taken to offer SMA carrier screening along with pre- and posttest education and genetic counseling to raise awareness and reduce misconceptions regarding SMA.

Application of multiplex competitive PCR combined with capillary electrophoresis in carrier screening of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive, fatal neurological disorder in children. The pathogenic gene of SMA is survival motor neuron1 (SMN1). There are many methods to detect SMN1 gene copy number, but few techniques are suitable for large-scale population screening. In order to find a rapid and accurate experimental technique for mass screening of SMA carriers in the population, the SMN1 gene copy number of 12 SMA patients and their parents was analyzed by multiplex competitive PCR combined with capillary electrophoresis. Meanwhile, the copy number of SMN1 gene in 151 healthy pregnant women in Jiangsu was screened with the MLPA technology to confirm their copy number of the SMN genes. The results showed that the 12 SMA patients had 0 copy of SMN1 gene, and all their parents had 1 copy of SMN1 gene only. Among 151 healthy subjects, 3 cases (2.0%) had 1 copy of SMN1 gene, and hence designated as SMA carriers. One hundred and thirty-four cases (88.7%) had 2 copies of the SMN1 gene. There were 14 cases (9.3%) with more than 2 copies of the SMN1 gene. Therefore, multiplex competitive PCR combined with capillary electrophoresis is a rapid, simple and accurate method for the detection of SMA carriers; and potentially applicable to mass screening of SMA carriers in the population.

Three Kinetic Patterns for the Oxidation of Emerging Organic Contaminants by Fe(VI): The Critical Roles of Fe(V) and Fe(IV).

For the first time, this study showed that the apparent second-order rate constants (kapp) of six selected emerging organic contaminants (EOCs) oxidation by Fe(VI) increased, remained constant, or declined with time, depending on [EOC]0/[Fe(VI)]0, pH, and EOCs species. Employing excess caffeine as the quenching reagent for Fe(V) and Fe(IV), it was found that Fe(V)/Fe(IV) contributed to 20-30% of phenol and bisphenol F degradation by Fe(VI), and the contributions of Fe(V)/Fe(IV) remained nearly constant with time under all the tested conditions. However, the contributions of Fe(V)/Fe(IV) accounted for over 50% during the oxidation of sulfamethoxazole, bisphenol S, and iohexol by Fe(VI), and the variation trends of kapp of their degradation by Fe(VI) with time displayed three different patterns, which coincided with those of the contributions of Fe(V)/Fe(IV) to their decomposition with time. Results of the quenching experiments were validated by simulating the oxidation kinetic data of methyl phenyl sulfoxide by Fe(VI), which revealed that the variation trends of kapp with time were significantly determined by the change in the molar ratio of Fe(V) to Fe(VI) with time, highlighting the key role of Fe(V) in the oxidative process. This study provides comprehensive and insightful information on the roles of Fe(V)/Fe(IV) during EOC oxidation by Fe(VI).

Enhanced Oxidation of Organic Contaminants by Iron(II)-Activated Periodate: The Significance of High-Valent Iron-Oxo Species.

Potassium periodate (PI, KIO4) was readily activated by Fe(II) under acidic conditions, resulting in the enhanced abatement of organic contaminants in 2 min, with the decay ratios of the selected pollutants even outnumbered those in the Fe(II)/peroxymonosulfate and Fe(II)/peroxydisulfate processes under identical conditions. Both 18O isotope labeling techniques using methyl phenyl sulfoxide (PMSO) as the substrate and X-ray absorption near-edge structure spectroscopy provided conclusive evidences for the generation of high-valent iron-oxo species (Fe(IV)) in the Fe(II)/PI process. Density functional theory calculations determined that the reaction of Fe(II) with PI followed the formation of a hydrogen bonding complex between Fe(H2O)62+ and IO4(H2O)-, ligand exchange, and oxygen atom transfer, consequently generating Fe(IV) species. More interestingly, the unexpected detection of 18O-labeled hydroxylated PMSO not only favored the simultaneous generation of ·OH but also demonstrated that ·OH was indirectly produced through the self-decay of Fe(IV) to form H2O2 and the subsequent Fenton reaction. In addition, IO4- was not transformed into the undesired iodine species (i.e., HOI, I2, and I3-) but was converted to nontoxic iodate (IO3-). This study proposed an efficient and environmental friendly process for the rapid removal of emerging contaminants and enriched the understandings on the evolution mechanism of ·OH in Fe(IV)-mediated processes.

Current attitudes and preconceptions towards expanded carrier screening in the Eastern Chinese reproductive-aged population.

PURPOSE: A growing number of Chinese individuals of reproductive age will face the choice of accepting or refusing expanded carrier screening (ECS). This study aimed to explore the awareness, wishes, and possible misconceptions of ECS among this population, as well as factors affecting their decision-making. METHODS: Chinese reproductive-aged individuals in Eastern China who sought cell-free fetal DNA screening and peripheral blood karyotype were invited to complete a 31-item ECS survey by scanning a specific quick response code. We evaluated the relationship between awareness, attitudes, and intentions to participate in ECS, along with possible misconceptions. RESULTS: Overall, 93.1% of participants intended to undergo ECS at their expenses, and 53.6% indicated they would pay less than 1000 CNY (approximately 145 USD) for the test. Around 96.5% of participants had misconceptions about ECS and genetic diseases. Participants whose first reaction was interest, who had prior awareness of the test, or who perceived benefits were more likely to intend to use ECS (p < 0.001). Participants with a bachelor's degree or above or with a household income over 150,000 CNY (approximately 21,700 USD) would be more likely to pay ≥ 1000 CNY (p < 0.05). CONCLUSIONS: Our study indicates that overall, the Eastern Chinese reproductive-aged population has positive attitudes towards ECS, although there are some misconceptions about ECS and genetic disorders. Population-based ECS appears to be desired by the reproductive-aged people in Eastern China. Steps should be taken to offer ECS along with pre- and post-test education and genetic counseling to raise awareness and to reduce misconceptions.

Insights into the Oxidation of Organic Cocontaminants during Cr(VI) Reduction by Sulfite: The Overlooked Significance of Cr(V).

Literature works reported that organic cocontaminants could be degraded during Cr(VI), a contaminant, reduction by sulfite (Cr(VI)/sulfite process). However, the role of Cr(V) and Cr(IV) intermediates in the Cr(VI)/sulfite process has been overlooked. In this study, we confirmed the generation of Cr(V) and proposed a new mechanism for the decomposition of coexisting organic contaminants during Cr(VI)/sulfite reactions occurring in oxygenated solutions at pHini 4.0 with the molar ratio of sulfite to Cr(VI) of 10.0. UV-visible and electron paramagnetic resonance (EPR) spectra indicate that Cr(V) was the predominant Cr intermediates in oxygenated solutions, while Cr(IV) accumulated in deoxygenated solutions. The contribution of Cr(V) to the degradation of organic contaminants was verified by the EPR spectra collected at 2 K and using methyl phenyl sulfoxide as a probe compound. Both Cr(V) and SO4•- contributed to the decomposition of organic contaminants in oxygenated solutions, with the relative contributions from each species being strongly dependent on properties of the target organic cocontaminants. The key mechanisms responsible for Cr(V) accumulation were supported by DFT calculations, and the degradation kinetics of organic cocontaminants was simulated with the program Kintecus 6.51. This work advances the fundamental understanding of the oxidative transformation of coexisting organic contaminants in this process.

Overlooked Role of Fe(IV) and Fe(V) in Organic Contaminant Oxidation by Fe(VI).

Fe(VI) has received increasing attention since it can decompose a wide range of trace organic contaminants (TrOCs) in water treatment. However, the role of short-lived Fe(IV) and Fe(V) in TrOC decomposition by Fe(VI) has been overlooked. Using methyl phenyl sulfoxide (PMSO), carbamazepine, and caffeine as probe TrOCs, we observed that the apparent second-order rate constants (kapp) between TrOCs and Fe(VI) determined with the initial kinetics data were strongly dependent on the initial molar ratios of TrOCs to Fe(VI). Furthermore, the kapp value increases gradually as the reaction proceeds. Several lines of evidence suggested that these phenomena were ascribed to the accumulation of Fe(IV) and Fe(V) arising from Fe(VI) decay. Kinetic models were built and employed to simulate the kinetics of Fe(VI) self-decay and the kinetics of PMSO degradation by Fe(VI). The modeling results revealed that PMSO was mainly degraded by Fe(IV) and Fe(V) rather than by Fe(VI) per se and Fe(V) played a dominant role, which was also supported by the density functional theory calculation results. Given that Fe(IV) and Fe(V) have much greater oxidizing reactivity than Fe(VI), this work urges the development of Fe(V)/Fe(IV)-based oxidation technology for efficient degradation of TrOCs.

Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole-exome sequencing.

BACKGROUND: In prenatal care, accumulating evidences has demonstrated that whole-exome sequencing (WES) expedites the genetic diagnosis of fetal structural anomalies. However, the clinical value of WES in the diagnosis of prenatal isolated congenital anomalies of the kidney and urinary tract (CAKUT) is unknown. METHODS: Forty-one fetuses with unexplained isolated CAKUT, normal karyotype and negative chromosomal microarray analysis (CMA) results, underwent WES and were accordingly grouped as (a) Group 1: complex cases with bilateral renal abnormalities (N = 19); and (b) Group 2: cases with isolated unilateral fetal renal abnormalities (N = 22). RESULTS: The detection rate of WES for pathogenic variants and incidental variants was 7.32% (3/41) and 2.4% (1/41), respectively. The three pathogenic variants were identified in the genes ACTA2 (multisystem smooth muscle dysfunction syndrome), PKHD1 (autosomal recessive form of polycystic kidney disease), and PKD1 (autosomal dominant polycystic kidney disease type 1). The incidental variants were detected in genes PPM1D (syndromic neurodevelopmental disorders). Furthermore, all above fetuses carrying pathogenic variants came from bilateral kidney anomalies. Thus, the detection rate was 0 for fetuses with unilateral fetal renal abnormalities and 15.7% (3/19) for bilateral renal abnormalities. CONCLUSION: This cohort shows that prenatal WES is a supplementary approach for the etiologic diagnosis of unexplained isolated CAKUT with negative CMA, especially for fetuses with bilateral renal abnormality.

Effects of carbon nanotubes on biodegradation of pollutants: Positive or negative?

Recently, a large quantity of carbon nanotubes (CNTs) enters the environment due to the increasing production and applications. More and more researches are focused on the fate and possible ecological risks of CNTs. Some literatures summarized the effects of CNTs on the chemical behavior and fate of pollutants. However, little reviewed the effects of CNTs on the biodegradation of pollutants. In general, the effects of CNTs on the biodegradation of pollutants and the related mechanisms were summarized in this review. CNTs have positive or negative effects on the biodegradation of contaminants by affecting the functional microorganisms, enzymes and the bioavailability of pollutants. CNTs may affect the microbial growth, activity, biomass, community composition, diversity and the activity of enzymes. The decrease of the bioavailability of pollutants due to the sorption on CNTs also causes the reduction of the biodegradation of contaminants. In addition, the roles of CNTs are controlled by multiple mechanisms, which are divided into three aspects i.e., properties of CNTs, environment condition, and microorganisms themself. The better understanding of the fate of CNTs and their impacts on the biochemical process in the environment is conducive to determine the release of CNTs into the environment.

Role of Ferrate(IV) and Ferrate(V) in Activating Ferrate(VI) by Calcium Sulfite for Enhanced Oxidation of Organic Contaminants.

Although the Fe(VI)-sulfite process has shown great potential for the rapid removal of organic contaminants, the major active oxidants (Fe(IV)/Fe(V) versus SO4•-/•OH) involved in this process are still under debate. By employing sparingly soluble CaSO3 as a slow-releasing source of SO32-, this study evaluated the oxidation performance of the Fe(VI)-CaSO3 process and identified the active oxidants involved in this process. The process exhibited efficient oxidation of a variety of compounds, including antibiotics, pharmaceuticals, and pesticides, at rates that were 6.1-173.7-fold faster than those measured for Fe(VI) alone, depending on pH, CaSO3 dosage, and the properties of organic contaminants. Many lines of evidence verified that neither SO4•- nor •OH was the active species in the Fe(VI)-CaSO3 process. The accelerating effect of CaSO3 was ascribed to the direct generation of Fe(IV)/Fe(V) species from the reaction of Fe(VI) with soluble SO32- via one-electron steps as well as the indirect generation of Fe(IV)/Fe(V) species from the self-decay of Fe(VI) and Fe(VI) reaction with H2O2, which could be catalyzed by uncomplexed Fe(III). Besides, the Fe(VI)-CaSO3 process exhibited satisfactory removal of organic contaminants in real water, and inorganic anions showed negligible effects on organic contaminant decomposition in this process. Thus, the Fe(VI)-CaSO3 process with Fe(IV)/Fe(V) as reactive oxidants may be a promising method for abating various micropollutants in water treatment.

Advances in applications of rhamnolipids biosurfactant in environmental remediation: A review.

The objective of this review is to provide a comprehensive overview of the advances in the applications of rhamnolipids biosurfactants in soil and ground water remediation for removal of petroleum hydrocarbon and heavy metal contaminants. The properties of rhamnolipids associated with the contaminant removal, that is, solubilization, emulsification, dispersion, foaming, wetting, complexation, and the ability to modify bacterial cell surface properties, were reviewed in the first place. Then current remediation technologies with integration of rhamnolipid were summarized, and the effects and mechanisms for rhamnolipid to facilitate contaminant removal for these technologies were discussed. Finally rhamnolipid-based methods for remediation of the sites co-contaminated by petroleum hydrocarbons and heavy metals were presented and discussed. The review is expected to enhance our understanding on environmental aspects of rhamnolipid and provide some important information to guide the extending use of this fascinating chemical in remediation applications.

Establishment of a proteome profile and identification of molecular markers for mouse spermatogonial stem cells.

Spermatogonial stem cells (SSCs) are undifferentiated cells that are required to maintain spermatogenesis throughout the reproductive life of mammals. Although SSC transplantation and culture provide a powerful tool to identify the mechanisms regulating SSC function, the precise signalling mechanisms governing SSC self-renewal and specific surface markers for purifying SSCs remain to be clearly determined. In the present study, we established a steady SSC culture according to the method described by Shinohara's lab. Fertile progeny was produced after transplantation of cultured SSCs into infertile mouse testis, and the red fluorescence exhibited by the culture cell membranes was stably and continuously transmitted to the offspring. Next, via advanced mass spectrometry and an optimized proteomics platform, we constructed the proteome profile, with 682 proteins expressed in SSCs. Furthermore bioinformatics analysis showed that the list contained several known molecules that are regulated in SSCs. Several nucleoproteins and membrane proteins were chosen for further exploration using immunofluorescence and RT-PCR. The results showed that SALL1, EZH2, and RCOR2 are possibly involved in the self-renewal mechanism of SSCs. Furthermore, the results of tissue-specific expression analysis showed that Gpat2 and Pld6 were uniquely and highly expressed in mouse testes and cultured SSCs. The cellular localization of PLD6 was further explored and the results showed it was primarily expressed in the spermatogonial membrane of mouse testes and cultured SSCs. The proteins identified in this study form the basis for further exploring the molecular mechanism of self-renewal in SSCs and for identifying specific surface markers of SSCs.

Effects of Cu2+, Ag+, and Pd2+ on the reductive debromination of 2,5-dibromoaniline by the ferrous hydroxy complex.

The ferrous hydroxy complex (FHC), composed of structural FeⅡ, has been shown to reduce a range of organic and inorganic contaminants. This study focused on the catalytic effects of Cu2+, Ag+, or Pd2+ on the reactivity of FHC suspensions towards 2,5-debromination (2,5-DBA). It was found that the target compound (2,5-DBA, 50 mg/L) could hardly be debrominated by FHC alone. However, Cu2+, Ag+, or Pd2+ had a significant promotion effect on the catalytic reactivity of structural FeⅡ on 2,5-DBA reduction. Pd2+ exhibited the best catalytic activity followed by Ag+ and Cu2+ in this study and the reductive debromination by Pd/FHC and Ag/FHC followed the pseudo-first-order kinetic model. Products distribution was highly dependent on the metal ions used. A reaction pathway was proposed in which the by-products were produced by hydrogenolysis and the elution order of bromines depended on the metal ions used. The enhanced reduction of 2,5-DBA by FHC suspensions modified by metal ions may prove useful in the development of improved materials for the treatment of halogenated organic compounds.

Establishment of a proteomic profile associated with gonocyte and spermatogonial stem cell maturation and differentiation in neonatal mice.

Initiation of the first wave of spermatogenesis in the neonatal mouse testis is characterized by differentiation of a transient population of germ cells called gonocytes in the center of the seminiferous tubules. After resuming mitotic activity, gonocytes relocate on the basement membrane, giving rise to spermatogonial stem cells (SSCs). These processes begin from birth in mice, and differentiated type A spermatogonia first appear by day 6 postpartum. During these processes, Sertoli cells within the seminiferous tubules and Leydig cells in the interstitial tissue form the stem cell "niche," and influence SSC fate decisions. Thus, we collected whole mouse testis tissues during the first wave of spermatogenesis at specific time points (days 0.5, 1.5, 2.5, 3.5, 4.5, and 5.5 postpartum) and constructed a comparative proteomic profile. We identified 252 differentially expressed proteins classified into three clusters based on expression, and bioinformatics analysis correlated each protein pattern to specific cell processes. Expression patterns of nine selected proteins were verified via Western blot, and cellular localizations of three proteins with little known information in testes were further investigated during spermatogenesis. Taken together, the results provide an important reference profile of a functional proteome during neonatal mouse gonocyte and SSC maturation and differentiation.

Lamin A/C proteins in the spermatid acroplaxome are essential in mouse spermiogenesis.

Spermiogenesis is a complex process of terminal differentiation that is necessary to produce mature sperm. Using protein expression profiles of mouse and human testes generated from our previous studies, we chose to examine the actions of lamin A/C in the current investigation. Lamin A and lamin C are isoforms of the A-type lamins that are encoded by the LMNA gene. Our results showed that lamin A/C was expressed in the mouse testis throughout the different stages of spermatogenesis and in mature sperm. Lamin A/C was also expressed in mouse haploid germ cells and was found to be localized to the acroplaxome in spermiogenesis, from round spermatids until mature spermatozoa. The decreased expression of lamin A/C following injections of siRNA against Lmna caused a significant increase in caudal sperm head abnormalities when compared with negative controls. These abnormalities were characterized by increased fragmentation of the acrosome and abnormal vesicles, which failed to fuse to the developing acrosome. This fragmentation also caused significant alterations in nuclear elongation and acrosome formation. Furthermore, we found that lamin A/C interacted with the microtubule plus-end-tracking protein CLIP170. These results suggest that lamin A/C is critical for proper structural and functional development of the sperm acrosome and head shape.

Construction and Validation of a Predictive Model for Coronary Artery Disease Using Extreme Gradient Boosting.

Purpose: Early recognition of coronary artery disease (CAD) could delay its progress and significantly reduce mortality. Sensitive, specific, cost-efficient and non-invasive indicators for assessing individual CAD risk in community population screening are urgently needed. Patients and Methods: 3112 patients with CAD and 3182 controls were recruited from three clinical centers in China, and differences in baseline and clinical characteristics were compared. For the discovery cohort, the least absolute shrinkage and selection operator (LASSO) regression was used to identify significant features and four machine learning algorithms (logistic regression, support vector machine (SVM), random forest (RF) and extreme gradient boosting (XGBoost)) were applied to construct models for CAD risk assessment, the receiver operating characteristics (ROC) curve and precision-recall (PR) curve were conducted to evaluate their predictive accuracy. The optimal model was interpreted by Shapley additive explanations (SHAP) analysis and assessed by the ROC curve, calibration curve, and decision curve analysis (DCA) and validated by two external cohorts. Results: Using LASSO filtration, all included variables were considered to be statistically significant. Four machine learning models were constructed based on these features and the results of ROC and PR curve implied that the XGBoost model exhibited the highest predictive performance, which yielded a high area of ROC curve (AUC) of 0.988 (95% CI: 0.986-0.991) to distinguish CAD patients from controls with a sensitivity of 94.6% and a specificity of 94.6%. The calibration curve showed that the predicted results were in good agreement with actual observations, and DCA exhibited a better net benefit across a wide range of threshold probabilities. External validation of the model also exhibited favorable discriminatory performance, with an AUC, sensitivity, and specificity of 0.953 (95% CI: 0.945-0.960), 89.9%, and 87.1% in the validation cohort, and 0.935 (95% CI: 0.915-0.955), 82.0%, and 90.3% in the replication cohort. Conclusion: Our model is highly informative for clinical practice and will be conducive to primary prevention and tailoring the precise management for CAD patients.